The Seventeen Kilodalton Protein (Skp) is a trimeric periplasmic chaperonethat assists outer membrane proteins in their folding and insertion intomembranes. Here we report the crystal structure of Skp from E. coli. Thestructure of the Skp trimer resembles a jellyfish with alpha-helicaltentacles protruding from a beta barrel body defining a central cavity.The architecture of Skp is unexpectedly similar to that of Prefoldin/GimC,a cytosolic chaperone present in eukaria and archea, that binds unfoldedsubstrates in its central cavity. The ability of Skp to prevent theaggregation of model substrates in vitro is independent of ATP. Skp caninteract directly with membrane lipids and lipopolysaccharide (LPS). Theseinteractions are needed for efficient Skp-assisted folding of membraneproteins. We have identified a putative LPS binding site on the outersurface of Skp and propose a model for unfolded substrate binding.